Removal of UK-donor deferral for variant Creutzfeldt-Jakob disease: A large donation gain in Australia.

BACKGROUND AND OBJECTIVES: Until 25 July 2022, people who spent more than 6 months in the United Kingdom during the variant Creutzfeldt-Jakob disease (vCJD) risk period 1980-1996 (UK donors) were deferred from blood donation in Australia. Regulatory approval to remove the deferral was underpinned by published mathematical modelling predicting negligible vCJD transmission risk increase with a gain of 58,000 donations. MATERIALS AND METHODS: The donor questionnaire retained the UK deferral screening question until a version update effective 12 February 2023, which enabled identification of the newly eligible cohort of UK donors. Their donations were tracked for a 6-month period (25 July 2022-24 January 2023) and compared with baseline Lifeblood donation metrics and predicted gains. RESULTS: A total of 38,462 UK donors attended to donate 78,762 times in the 6 months. Of these, 32,358 donors (females = 19,456, males = 12,902) successfully donated 67,914 times representing 8.4% of total collections. CONCLUSION: Cessation of the UK deferral resulted in donation gains exceeding modelled predictions because of a higher than predicted number of donors who donated at a higher rate. Had these newly eligible donors not donated, overall donation numbers would have been 88% of target rather than the 96% achieved.

Perceived risk of HIV transmission by blood transfusion among gay, bisexual, and other men who have sex with men (gbMSM) in Australia.

BACKGROUND: In Australia, men who have sex with men (MSM) are deferred from blood donation for 3 months from last sexual contact. Internationally, deferral policies for MSM are evolving in the direction of expanded inclusivity in response to community expectations. To inform future policy options, we assessed perceptions of the risk of HIV transmission from blood transfusion among Australian MSM. STUDY DESIGN AND METHODS: Flux is an online prospective cohort of Australian gay and bisexual men (cis or trans, regardless of their sexual history) and other men who have had sex with men (gbMSM). We included questions on blood donation rules, window period (WP) duration, infectivity of blood from people with HIV on treatment and attitudes to more detailed questioning of sexual practices in the regular survey of Flux participants and conducted a descriptive analysis of responses. RESULTS: Of 716 Flux participants in 2019, 703 responded to the blood donation questions. The mean age was 43.7 years (SD 13.6 years). Overall, 74% were willing to confidentially respond to specific sexual behavior questions, such as the last time they had sex and the type of sex they had, in order to be considered eligible to donate blood. The majority (92%) of participants correctly assessed the duration of the WP as less than 1 month. When asked whether transfusion of blood from a donor with HIV and an undetectable viral load could transmit HIV, just under half (48%) correctly said yes. CONCLUSION: Our study suggests Australian gbMSM are generally comfortable with answering more detailed questions regarding sexual activity during the assessment to donate, indicating they would do so honestly. gbMSM are knowledgeable about the WP duration, important for their ability to correctly self-assess their HIV risk. However, half of participants incorrectly assessed the transmissibility by blood transfusion from an HIV positive person with an undetectable viral load, suggesting the need for a targeted education campaign.

Removing hepatitis C antibody testing for Australian blood donations: A cost-effectiveness analysis.

BACKGROUND AND OBJECTIVES: The risk of transfusion-transmitted hepatitis C virus (HCV) infections is extremely low in Australia. This study aims to conduct a cost-effectiveness analysis of different testing strategies for HCV infection in blood donations. MATERIALS AND METHODS: The four testing strategies evaluated in this study were universal testing with both HCV antibody (anti-HCV) and nucleic acid testing (NAT); anti-HCV and NAT for first-time donations and NAT only for repeat donations; anti-HCV and NAT for transfusible component donations and NAT only for plasma for further manufacture; and universal testing with NAT only. A decision-analytical model was developed to assess the cost-effectiveness of alternative HCV testing strategies. Sensitivity analysis and threshold analysis were conducted to account for data uncertainty. RESULTS: The number of potential transfusion-transmitted cases of acute hepatitis C and chronic hepatitis C was approximately zero in all four strategies. Universal testing with NAT only was the most cost-effective strategy due to the lowest testing cost. The threshold analysis showed that for the current practice to be cost-effective, the residual risks of other testing strategies would have to be at least 1 HCV infection in 2424 donations, which is over 60,000 times the baseline residual risk (1 in 151 million donations). CONCLUSION: The screening strategy for HCV in blood donations currently implemented in Australia is not cost-effective compared with targeted testing or universal testing with NAT only. Partial or total removal of anti-HCV testing would bring significant cost savings without compromising blood recipient safety.

Recently Acquired Blood-borne Virus Infections in Australian Deceased Organ Donors: Estimation of the Residual Risk of Unexpected Transmission.

Unexpected donor-derived infections of hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV are rare but important potential complications of deceased organ transplantation. The prevalence of recently acquired (yield) infections has not been previously described in a national cohort of Australian deceased organ donors. Donor yield infections are of particularly significance, as they can be used to gain insights in the incidence of disease in the donor pool and in turn, estimate the risk of unexpected disease transmission to recipients. Methods: We conducted a retrospective review of all patients who commenced workup for donation in Australia between 2014 and 2020. Yield cases were defined by having both unreactive serological screening for current or previous infection and reactive nucleic acid testing screening on initial and repeat testing. Incidence was calculated using a yield window estimate and residual risk using the incidence/window period model. Results: The review identified only a single yield infection of HBV in 3724 persons who commenced donation workup. There were no yield cases of HIV or HCV. There were no yield infections in donors with increased viral risk behaviors. The prevalence of HBV, HCV, and HIV was 0.06% (0.01-0.22), 0.00% (0-0.11), and 0.00% (0-0.11), respectively. The residual risk of HBV was estimated to be 0.021% (0.001-0.119). Conclusions: The prevalence of recently acquired HBV, HCV, and HIV in Australians who commence workup for deceased donation is low. This novel application of yield-case-methodology has produced estimates of unexpected disease transmission which are modest, particularly when contrasted with local average waitlist mortality. Supplemental Visual Abstract; http://links.lww.com/TXD/A503.

West Nile virus transfusion-transmission risk in Australia associated with a seasonal outbreak in the United States.

BACKGROUND: West Nile virus (WNV) is a potentially transfusion-transmissible virus endemic in the US. The aim of this study was to estimate the monthly WNV transfusion transmission (TT) risk in Australia associated with donors returning from the US in 2018 and consider the implications for mitigation strategies. STUDY DESIGN AND METHODS: We used a probabilistic risk model to estimate the monthly WNV TT risks for each outbreak state/district in the US for the 2018 transmission season and the cumulative monthly risk for all US states/districts. RESULTS: The highest monthly cumulative transfusion risk in Australia occurred in August 2018 when 746 West Nile neuroinvasive disease cases were reported in the US and the estimated mean WNV TT risk in Australia was 1 in 1.0 × 108 donations (95% confidence interval [CI]: 1.6 × 108 -7.0 × 107 ). The highest risk during August was associated with California, with a mean risk of 1 in 4.1 × 108 donations (95% CI: 2.9 × 108 -6.6 × 108 ), representing 24% of the total risk in Australia. The cumulative TT risk in Australia for the other 11 months varied from 1 in 1.5 × 108 donations (95% CI: 2.3 × 108 -1.0 × 108 ) in September to 1 in 3.9 × 1010 donations (95% CI: 6.1 × 1010 -2.7 × 1010 ) in February. DISCUSSION: Our modeling indicates that the WNV TT risk in Australia associated with seasonal outbreaks in the US is extremely small and may not warrant donation restrictions for donors returning from the US.

An Outbreak of Japanese Encephalitis Virus in Australia; What Is the Risk to Blood Safety?

A widespread outbreak of Japanese encephalitis virus (JEV) was detected in mainland Australia in 2022 in a previous non-endemic area. Given JEV is known to be transfusion-transmissible, a rapid blood-safety risk assessment was performed using a simple deterministic model to estimate the risk to blood safety over a 3-month outbreak period during which 234,212 donors attended. The cumulative estimated incidence in donors was 82 infections with an estimated 4.26 viraemic components issued, 1.58 resulting in transfusion-transmission and an estimated risk of encephalitis of 1 in 4.3 million per component transfused over the risk period. Australia has initiated a robust public health response, including vector control, animal control and movement, and surveillance. Unlike West Nile virus, there is an effective vaccine that is being rolled-out to those at higher risk. Risk evaluation considered options such as restricting those potentially at risk to plasma for fractionation, which incorporates additional pathogen reduction, introducing a screening test, physicochemical pathogen reduction, quarantine, post donation illness policy changes and a new donor deferral. However, except for introducing a new deferral to potentially cover rare flavivirus risks, no option resulted in a clear risk reduction benefit but all posed threats to blood sufficiency or cost. Therefore, the blood safety risk was concluded to be tolerable without specific mitigations.

Severe Acute Respiratory Syndrome Coronavirus 2 and Blood Safety: An Updated Review.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus first identified in late 2019 and subsequently declared a worldwide pandemic in March 2020. In this review, we provide an overview of the implications of SARS-CoV-2 for blood safety and sufficiency. Summary: Approximately one-third of SARS-CoV-2 infections are asymptomatic. The reported mean incubation period typically varies from 2 to 11 days, but longer periods up to 22 days have been reported. The blood phase of SARS-CoV-2 appears to be brief and low level, with RNAaemia detectable in only a small proportion of patients, typically associated with more severe disease and not demonstrated to be infectious virus. A small number of presymptomatic and asymptomatic blood phase cases have been reported. Transfusion-transmission (TT) of SARS-CoV-2 has not been reported. Therefore, the TT risk associated with SARS-CoV-2 is currently theoretical. To mitigate any potential TT risk, but more importantly to prevent respiratory transmission in donor centers, blood services can implement donor deferral policies based on travel, disease status, or potential risk of exposure and encourage staff vaccination. Key Messages: The TT risk of SARS-CoV-2 appears to be low. The biggest risk to blood services in the current COVID-19 pandemic is to maintain the sufficiency of the blood supply while minimizing respiratory transmission of SARS-CoV-2 to donors and staff while donating blood.

Risk of variant Creutzfeldt-Jakob disease transmission by blood transfusion in Australia.

BACKGROUND AND OBJECTIVES: Most of the 233 worldwide cases of variant Creutzfeldt-Jakob disease (vCJD) have been reported in the United Kingdom and 3 have been associated with transfusion-transmission. To mitigate the potential vCJD risk to blood safety, Australian Red Cross Lifeblood imposes restrictions on blood donation from people with prior residency in, or extended travel to, the United Kingdom during the risk period 1980-1996. We have modified a previously published methodology to estimate the transfusion-transmission risk of vCJD associated with fresh component transfusion in Australia if the UK residence deferral was removed. MATERIALS AND METHODS: The prevalence of current pre-symptomatic vCJD infection in the United Kingdom by age at infection and genotype was estimated based on risk of exposure to the bovine spongiform encephalopathy agent for the period 1980-1996. These results were used to estimate the age-specific prevalence of undiagnosed, pre-symptomatic vCJD in the Australian population in the current year due to prior UK residency or travel. The primary model outputs were the 2020 vCJD risks/unit of vCJD contamination, transfusion-transmission (infections) and clinical cases. RESULTS: The overall (prior UK residency in and travel to United Kingdom, 1980-1996) mean risk of contamination per unit was 1 in 29,900,000. The risks of resulting vCJD transmission (infection) and clinical case were 1 in 389,000,000 and 1 in 1,450,000,000, respectively. CONCLUSION: Our modelling suggests that removing the Lifeblood donation deferral for travel to, or UK residence, would result in virtually no increased risk of vCJD transfusion-transmission and would be a safe and effective strategy for increasing the donor base.

Current challenges of severe acute respiratory syndrome coronavirus 2 seroprevalence studies among blood donors: A scoping review.

BACKGROUND AND OBJECTIVES: Blood donors are increasingly being recognized as an informative resource for surveillance. We aimed to review severe acute respiratory syndrome coronavirus 2 seroprevalence studies conducted among blood donors to investigate methodological biases and provide guidance for future research. MATERIALS AND METHODS: We conducted a scoping review of peer-reviewed and preprint publications between January 2020 and January 2021. Two reviewers used standardized forms to extract seroprevalence estimates and data on methodology pertaining to population sampling, periodicity, assay characteristics, and antibody kinetics. National data on cumulative incidence and social distancing policies were extracted from publicly available sources and summarized. RESULTS: Thirty-three studies representing 1,323,307 blood donations from 20 countries worldwide were included (sample sizes ranged from 22 to 953,926 donations). The majority of the studies (79%) reported seroprevalence rates <10% (ranging from 0% to 76% [after adjusting for waning antibodies]). Overall, less than 1 in 5 studies reported standardized seroprevalence rates to reflect the demographics of the general population. Stratification by age and sex were most common (64% of studies), followed by region (48%). A total of 52% of studies reported seroprevalence at a single time point. Overall, 27 unique assay combinations were identified, 55% of studies used a single assay and only 39% adjusted seroprevalence rates for imperfect test characteristics. Among the nationally representative studies, case detection was most underrepresented in Kenya (1:1264). CONCLUSION: By the end of 2020, seroprevalence rates were far from reaching herd immunity. In addition to differences in community transmission and diverse public health policies, study designs and methodology were likely contributing factors to seroprevalence heterogeneity.

HIV residual risk in Canada for apheresis source plasma donation without deferral for men who have sex with men.

BACKGROUND AND OBJECTIVES: In Canada, men having sex with men (MSM) are deferred for 3 months from last sexual contact to reduce human immunodeficiency virus (HIV) risk to recipients. The aim of this paper was to model the Canadian residual risk of HIV-positive source plasma incorporating pathogen inactivation (PI) under no MSM deferral scenarios for apheresis plasma donations. MATERIALS AND METHODS: A combined Bayesian network (BN) and Monte Carlo approach were implemented to estimate the HIV residual risk under 3-month deferral compared with no deferral without quarantine scenarios for MSM donors. Models involve the stochastic generation of donation and its infection status based on its corresponding simulated donor profile. Viral load reduction conferred by PI used by source plasma fractionators was simulated. Model parameters were derived from Héma-Québec and Canadian Blood Services data, viral loads in a large sample of HIV-positive US blood donors, CSL Behring documentation and from published data. RESULTS: In the most likely scenario for the 3-month deferral model, there were 2.71 positive donations per 1,000,000 donations (95% confidence interval [CI] 2.63-2.78). For the no-deferral model, there were 3.01 positive donations per 1,000,000 donations (95% CI 2.94-3.09). For both scenarios, the risk of having an infectious pool was 0 in 300,000 pools (95% CI 0-0.0000123) after consideration of PI. CONCLUSION: Based on simulation results, there would be a negligible HIV residual risk associated with the removal of a time-based MSM deferral without quarantine for source plasma incorporating PI.

A Systematic Review of Interventions Used to Increase Blood Donor Compliance with Deferral Criteria.

BACKGROUND AND OBJECTIVES: Pre-donation screening of potential blood donors is critical for ensuring the safety of the donor blood supply, and donor deferral as a result of risk factors is practised worldwide. This systematic review was conducted in the context of an expert review convened by the Australian Red Cross Lifeblood in 2013 to consider Lifeblood's injecting drug use (IDU)-related policies and aimed to identify studies assessing interventions to improve compliance with deferral criteria in blood donation settings. MATERIALS AND METHODS: MEDLINE/PubMed, OVID Medline, OVID Embase, LILACS, and the Cochrane Library (CENTRAL and DARE) databases were searched for studies conducted within blood donation settings that examined interventions to increase blood donor compliance with deferral criteria. Observational and experimental studies from all geographical areas were considered. RESULTS: Ten studies were identified that tested at least one intervention to improve blood donor compliance with deferral criteria, including computerized interviews or questionnaires, direct and indirect oral questioning, educational materials, and a combination of a tickbox questionnaire and a personal donor interview. High-quality evidence from a single study was provided for the effectiveness of a computerized interview in improving detection of HIV risk behaviour. Low-quality evidence for the effectiveness of computerized interviews was provided by 3 additional studies. Two studies reported a moderate effect of direct questioning in increasing donor deferral, but the quality of the evidence was low. CONCLUSION: This review identified several interventions to improve donor compliance that have been tested in blood donation settings and provided evidence for the effectiveness of computerized interviews in improving detection of risk factors.

Endoscopies, blood-borne viruses and blood donors: time to move on from precaution.

BACKGROUND AND OBJECTIVES: Based on the Council of Europe directive which dictates regulatory requirements in Australia, blood donors are currently deferred from donating for 4 months after an endoscopic procedure if either polyps were removed or a biopsy sample was taken. We aimed to assess the incidence of blood-borne viruses (BBVs) (HIV, hepatitis B and C) in blood donors who donated after an endoscopic procedure and evaluate the risk to blood safety through risk modelling. MATERIALS AND METHODS: Donors from 1/1/2013 to 31/12/2017 with an endoscopy deferral on their blood donor file with pre- and post-BBV testing were analysed to determine an incidence of BBVs using standard methods. The standard blood donor cohort was used as a comparator group. Using the incidence of endoscopies and BBV risk, the total residual risk estimate of allowing donors to return postendoscopy without restriction was calculated. RESULTS: The incidence of a BBV postendoscopy in this large cohort of 16,283 where testing has been confirmed postendoscopy was zero (95% CI 0-0·000105). The upper confidence interval of the zero events is 10·5 per 100 000 donations. Total positive donations from 2017 repeat donors were 1·87 per 100 000 (95% CI 0·0000117-0·0000277). Sensitivity analysis demonstrated that the residual risk remained negligible under realistic worst-case scenarios. CONCLUSION: A BBV endoscopy deferral is not required for blood safety in Australia. The presented data has enabled us to submit a request for an exemption to our regulator, which has been approved and the policy change subsequently implemented by Lifeblood on 4/4/2020.

Severe acute respiratory syndrome coronavirus-2: implications for blood safety and sufficiency.

BACKGROUND AND OBJECTIVE: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus, first identified in China at the end of 2019 and has now caused a worldwide pandemic. In this review, we provide an overview of the implications of SARS-CoV-2 for blood safety and sufficiency. MATERIAL AND METHOD: We searched the PubMed database, the preprint sites bioRxiv and medRxiv, the websites of the World Health Organization, European Centre for Disease Prevention and Control, the US Communicable Diseases Center and monitored ProMed updates. RESULTS: An estimated 15%-46% of SARS-CoV-2 infections are asymptomatic. The reported mean incubation period is 3 to 7 days with a range of 1-14 days. The blood phase of SARS-CoV-2 appears to be brief and low level, with RNAaemia detectable in only a small proportion of patients, typically associated with more severe disease and not demonstrated to be infectious virus. An asymptomatic blood phase has not been demonstrated. Given these characteristics of SARS-CoV-2 infection and the absence of reported transfusion transmission (TT), the TT risk is currently theoretical. To mitigate any potential TT risk, but more importantly to prevent respiratory transmission in donor centres, blood centres can implement donor deferral policies based on travel, disease status or potential risk of exposure. CONCLUSION: The TT risk of SARS-CoV-2 appears to be low. The biggest risk to blood services in the current COVID-19 pandemic is to maintain the sufficiency of the blood supply while minimizing respiratory transmission of SARS-CoV-19 to donors and staff while donating blood.

Effect of HIV pre-exposure prophylaxis (PrEP) on detection of early infection and its impact on the appropriate post-PrEP deferral period.

INTRODUCTION: HIV antivirals for pre-exposure prophylaxis (PrEP) are known to affect detection of early HIV infection through suppression of viral load and delayed seroconversion. To cover potential delay in HIV detection associated with PrEP use by blood donors in the context of international reductions in sexual activity-based deferral periods, we analysed the available data to determine the appropriate minimum post-PrEP deferral period for blood donation. MATERIALS AND METHODS: Published cases of incident HIV infection when PrEP use was objectively demonstrable were identified, consisting principally of seroconverters from the Partners PrEP study (a clinical trial of PrEP efficacy). Data were reviewed to determine the impact of PrEP on the detection of HIV RNA, p24 Ag and seroconversion delay. RESULTS: Nucleic acid testing (NAT) detected early HIV infection in the presence of PrEP prior to or in concordance with serological testing in approximately 90% of cases. Undetectable HIV RNA would rebound to detectable levels within two months of PrEP cessation. PrEP delayed p24 antigen detection and antibody seroconversion by about 7 days. CONCLUSION: Even when daily PrEP is continued, it is likely that the majority of early HIV infections are detectable by individual donation (ID)-NAT, with p24 Ag or antibody seroconversion occurring conservatively within four weeks of exposure. HIV RNA levels also rebound rapidly in the absence of PrEP. In Australia, a three-month deferral period for blood donation after the last dose of PrEP provides an appropriate safety margin to mitigate the residual risk of transfusion-transmitted HIV.

Modeling the West Nile virus transfusion transmission risk in a nonoutbreak country associated with traveling donors.

BACKGROUND: West Nile virus (WNV) is a mosquito-borne virus and transfusion transmission (TT) has been demonstrated. The European Union and neighboring countries experience an annual transmission season. STUDY DESIGN AND METHODS: We developed a novel probabilistic model to estimate the WNV TT risk in Australia attributable to returned donors who had travelled to the European Union and neighboring countries during the 2018. We estimated weekly WNV TT risks in Australia for each outbreak country and the cumulative risk for all countries. RESULTS: Highest mean weekly TT risk in Australia attributable to donors returning from a specific outbreak country was 1 in 23.3 million (plausible range, 16.8-41.9 million) donations during Week 39 in Croatia. Highest mean weekly cumulative TT risk was 1 in 8.5 million donations (plausible range, 5.1-17.8 million) during Week 35. CONCLUSIONS: The estimated TT risk in Australia attributable to returning donors from the European Union and neighboring countries in 2018 was very small, and additional risk mitigation strategies were not indicated. In the context of such low TT risks, a simpler but effective approach would be to monitor the number of weekly reported West Nile fever cases and implement risk modeling only when the reported cases reached a predefined number or trigger point.

Attitudes and willingness to donate blood among gay and bisexual men in Australia.

BACKGROUND: Men who have sex with men in Australia are currently ineligible to donate blood (are "deferred") for 12 months since last oral or anal sexual contact with another man. In Australia and overseas, there has been limited research on attitudes and perceptions related to blood donation in this population. STUDY DESIGN AND METHODS: Questions on blood donation histories and attitudes toward the deferral policy were included in the questionnaire of an online prospective cohort of gay and bisexual men (GBM) living in Australia. RESULTS: In 2018, 1595 GBM responded to the survey. In this sample, 28.7% reported previously donating blood. Among the remaining men who had never donated blood, 64.5% expressed an interest in doing so. Nearly all men indicated they were not willing to abstain from sex with another man for 12 months in order to donate, and the vast majority believed the rule was unfair, too strict, and homophobic. Three-quarters (77.7%) said that if the policy changed, they would likely donate blood. Age and openness about one's sexuality were independently associated with one's willingness to donate blood in the absence of the deferral. CONCLUSION: There was a high level of willingness and desire to donate blood among GBM. However, rather than abstaining from sex in order to donate, many men comply with the deferral policy and do not donate. A less conservative deferral policy may increase donations from GBM.